Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

• Published in: Molecular psychiatry Vol. 13; no. 3; pp. 313 - 324
• Main Authors: Buckholtz, J W, Callicott, J H, Kolachana, B, Hariri, A R, Goldberg, T E, Genderson, M, Egan, M F, Mattay, V S, Weinberger, D R, Meyer-Lindenberg, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2008; Nature Publishing Group
• Subjects: Adult; Amine oxidase (flavin-containing); Amygdala; Amygdala (Brain); Antisocial personality disorder; Arousal; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain Mapping; Brain research; Cortex (cingulate); Emotion regulation; Emotional behavior; Evaluation; Facial Expression; Female; Genes; Genetic aspects; Genetic control; Genetic diversity; Genetic Variation; Health aspects; Humans; Image Processing, Computer-Assisted; Individuality; Influence; Magnetic Resonance Imaging; Male; Medical sciences; Medicine; Medicine & Public Health; Mental disorders; Mental health; Models, Biological; Monoamine oxidase; Monoamine Oxidase - genetics; Neural circuitry; Neural Pathways - blood supply; Neural Pathways - physiology; Neuroimaging; Neuropsychological Tests; Neurosciences; original-article; Oxygen - blood; Personality; Personality - genetics; Personality tests; Personality traits; Pharmacotherapy; Photic Stimulation - methods; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - blood supply; Prefrontal Cortex - physiology; Properties; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychosis; Reinforcement; Serotonin; Social behavior; United States; United States > US; fMRI; emotion regulation; amygdala; functional connectivity; antisocial; effective connectivity; cingulate; Affect affectivity; Genetic variability; Amygdala; Central nervous system; Genetic determinism; Encephalon; Cingulate cortex; Genetics; Amygdaloid nucleus; Human; Antisocial behavior; Basal ganglion; Emotion emotionality; Personality; Prefrontal cortex; Nuclear magnetic resonance imaging; Interindividual comparison; Medical imagery; Self regulation; Social behavior disorder; Functional imaging
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/sj.mp.4002020

Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC–amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.